OSWG Recommended Approaches to the Nonclinical Pharmacokinetic (Absorption, Distribution, Metabolism, and Excretion) Characterization of Therapeutic Oligonucleotides

被引：6

作者：

Berman, Cindy L. ^{[1
,16
]}

Antonsson, Madeleine ^{[2
]}

Batkai, Sandor ^{[3
]}

Bosgra, Sieto

Chopda, Girish R. ^{[4
]}

Driessen, Wouter ^{[5
]}

Foy, Jeffrey ^{[6
]}

Hassan, Chopie ^{[7
]}

Hu, Xiao Shelley ^{[8
]}

Jang, Hyun Gyung ^{[8
]}

Meena ^{[9
]}

Sanseverino, Mark ^{[10
]}

Thum, Thomas ^{[3
,11
,12
]}

Wang, Yanfeng ^{[13
]}

Wild, Martin ^{[14
]}

Wu, Jing-Tao ^{[15
]}

机构：

[1] Berman Consulting, Wayland, MA USA

[2] AstraZeneca, Early CVRM, Biopharmaceut R&D, Gothenburg, Sweden

[3] Cardior Pharmaceut GmbH, Hannover, Germany

[4] Novo Nordisk Co, Dicerna Pharmaceut Inc, Lexington, MA USA

[5] Anjarium Biosci AG, Zurich, Switzerland

[6] PepGen Inc, Cambridge, MA USA

[7] ProQR Therapeut NV, Leiden, Netherlands

[8] Wave Life Sci, Cambridge, MA USA

[9] Stoke Therapeut, Bedford, MA USA

[10] Agilent Therapeut, Boulder, CO USA

[11] Inst Mol & Translat Therapeut Strategies IMTTS, Hannover, Germany

[12] Fraunhofer Inst Toxicol & Expt Med, Hannover, Germany

[13] Ionis Pharmaceut, Carlsbad, CA USA

[14] AstraZeneca, Early Oncol, Oncol R&D, Cambridge, England

[15] Alnylam Pharmaceut, Cambridge, MA USA

[16] Berman Consulting, Wayland, MA 01778 USA

来源：

NUCLEIC ACID THERAPEUTICS | 2023年 / 33卷 / 05期

关键词：

ADME; ASO; siRNA; OSWG; oligonucleotides; pharmacokinetics; PLASMA-PROTEIN BINDING; ANTISENSE OLIGONUCLEOTIDE; ASSAY; ANALOGS;

D O I：

10.1089/nat.2023.0011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

This white paper summarizes the recommendations of the absorption, distribution, metabolism, and excretion (ADME) Subcommittee of the Oligonucleotide Safety Working Group for the characterization of absorption, distribution, metabolism, and excretion of oligonucleotide (ON) therapeutics in nonclinical studies. In general, the recommended approach is similar to that for small molecule drugs. However, some differences in timing and/or scope may be warranted due to the greater consistency of results across ON classes as compared with the diversity among small molecule classes. For some types of studies, a platform-based approach may be appropriate; once sufficient data are available for the platform, presentation of these data should be sufficient to support development of additional ONs of the same platform. These recommendations can serve as a starting point for nonclinical study design and foundation for discussions with regulatory agencies.

引用

页码：287 / 305

页数：19

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